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Major Cardiovascular Events in Patients with Gout and Associated Cardiovascular Disease or Heart Failure and Chronic
JoAnne Foody1, Robin S Turpin2, Beni A Tidwell3
1Associate Professor, Harvard Medical School, Boston, MA, and Executive Director-Cardiovascular, Janssen Pharmaceuticals, New Brunswick, NJ.
Insights
Febuxostat treatment significantly reduced major cardiovascular events in gout patients with chronic kidney disease (CKD) and cardiovascular disease (CVD) or heart failure (HF) compared to allopurinol.
Area of Science:
- Nephrology
- Cardiology
- Rheumatology
Background:
- Observational studies suggest treating hyperuricemia in gout patients with moderate-to-severe chronic kidney disease (CKD) may improve renal and cardiovascular (CV) outcomes.
- Gout management in patients with CKD and comorbid CV disease (CVD) or heart failure (HF) requires careful consideration of urate-lowering therapies.
Purpose of the Study:
- To evaluate the real-world impact of initiating allopurinol versus febuxostat on major CV events.
- To assess the safety and efficacy of these treatments in a specific patient population with gout, CKD, and CVD or HF.
Main Methods:
- Retrospective cohort study using MarketScan databases (2009-2013).
- Included patients (>18 years) with gout, stage 3-4 CKD, and pre-existing CVD or HF.
- Compared major CV events (CAD, cerebrovascular, PVD) between allopurinol and febuxostat initiators using Cox proportional hazards modeling.
Main Results:
- Febuxostat initiation was associated with a significantly lower risk of major CV events compared to allopurinol (HR, 0.52; P=.02).
- Rates of major CV events per 1000 person-years were 51.8 for febuxostat vs. 99.3 for allopurinol.
- The benefit was largely driven by a reduction in peripheral vascular disease (PVD)-specific events (P=.026).
Conclusions:
- Febuxostat treatment demonstrated a significantly lower rate of major CV events in patients with moderate-to-severe CKD and CVD or HF compared to allopurinol.
- This real-world evidence supports febuxostat as a potentially preferred option for managing hyperuricemia in this high-risk patient group.
Background:
Several observational studies and meta-analyses have suggested that treating hyperuricemia in patients with gout and moderate or severe chronic kidney disease (CKD) may improve renal and cardiovascular (CV) outcomes.
Objective:
To evaluate the impact of initiating allopurinol or febuxostat treatment on major CV events in patients with gout, preexisting CV disease (CVD) or heart failure (HF), and stage 3 or 4 CKD in a real-world setting.
Methods:
Patients with gout (aged >18 years) who initiated allopurinol or febuxostat treatment between 2009 and 2013 after a diagnosis of stage 3 or 4 CKD and CVD-including coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD)-or HF were selected from the MarketScan databases. The major CV events included CAD-specific, cerebrovascular disease-specific, and PVD-specific events. Cox proportional hazards modeling identified the predictors of major CV events in aggregate, and of CAD, cerebrovascular disease, and PVD events, individually.
Results:
During follow-up, 2426 patients (370 receiving febuxostat and 2056 receiving allopurinol; 63% male; mean age, 73 years) had 162 major CV events (3.8% in those receiving febuxostat vs 7.2% in those receiving allopurinol; P = .015). The rates of major CV events per 1000 person-years were 51.8 (95% confidence interval [CI], 28-87) in patients initiating febuxostat and 99.3 (95% CI, 84-117) among those initiating allopurinol. Overall, 49.4% of patients had a CAD event, 32.5% had a PVD event, and 23.5% had a cerebrovascular disease-specific event. Febuxostat initiation was associated with a significantly lower risk for a major CV event versus patients who initiated allopurinol (hazard ratio, 0.52; P = .02), driven in large part by lower PVD-specific events (P = .026).
Conclusion:
Patients with moderate-to-severe CKD and CVD or HF who initiated febuxostat treatment had a significantly lower rate of major CV events than patients who initiated allopurinol.
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